SUMOylation of the lysine-less tumor suppressor p14ARF counters ubiquitylation-dependent degradation.

p14ARF is a lysine-less tumor suppressor that enhances SUMOylation of its interactors. Although p14ARF is known to interact with the E2 SUMO conjugating enzyme UBC9, the link between ARF and SUMOylation is poorly understood and the potential impact of SUMOylation on p14ARF is unknown. Here we show that SUMO2 conjugates to the N-terminus of p14ARF and stabilizes it.

Transcriptional repression of SOX2 by p53 in cancer cells regulates cell identity and migration.

During cancer development and progression, many genetic alterations lead to the acquisition of novel features that confer selective advantage to cancer cells and that resemble developmental programs. SRY-box transcription factor 2 (SOX2) is one of the key pluripotency transcription factors, expressed during embryonic development and active in adult stem cells. In cancer, SOX2 is frequently dysregulated and associated with tumor stemness and poor patient survival.

A role for NFIB in downregulation and epigenome accessibility changes due to long-term estrogen treatment of breast cancer epithelial cells.

Estrogen (E2) regulates the differentiation and proliferation of mammary progenitor cells by modulating the transcription of multiple genes. One of the genes that is downregulated by E2 is , a transcription factor associated with stem and progenitor cells that is overexpressed during breast tumourigenesis. To elucidate the mechanisms underlying E2-mediated repression, we investigated epigenome and transcriptome changes following short- and long-term E2 exposure in breast cancer cells.

Inhibition of lung tumorigenesis by transient reprogramming in cancer cells.

Oncogenic transformation and Oct4, Sox2, Klf4 and c-Myc (OSKM)-mediated induction of pluripotency are two independent and incompatible cellular fates. While continuous expression of OSKM can convert normal somatic cells into teratogenic pluripotent cells, it remains speculative what is the impact of transient OSKM expression in cancer cells. Here, we find that OSKM expression limits the growth of transformed lung cells by inducing apoptosis and senescence.

Correction: Limited Role of Murine ATM in Oncogene-Induced Senescence and p53-Dependent Tumor Suppression.

[This corrects the article DOI: 10.1371/journal.pone.

Epigenetic reprogramming of a distal developmental enhancer cluster drives SOX2 overexpression in breast and lung adenocarcinoma.

Enhancer reprogramming has been proposed as a key source of transcriptional dysregulation during tumorigenesis, but the molecular mechanisms underlying this process remain unclear. Here, we identify an enhancer cluster required for normal development that is aberrantly activated in breast and lung adenocarcinoma. Deletion of the SRR124-134 cluster disrupts expression of the SOX2 oncogene, dysregulates genome-wide transcription and chromatin accessibility and reduces the ability of cancer cells to form colonies in vitro.

Current Risk of Dirofilariosis Transmission in the Iberian Peninsula (Spain and Portugal) and the Balearic Islands (Spain) and Its Future Projection under Climate Change Scenarios.

Dirofilariosis is a vector-borne zoonotic disease whose distribution is linked to the presence of culicid mosquitoes. Spain and Portugal are considered endemic countries; however, the distribution of dirofilariosis is not uniform. Our aim was to develop a more accurate risk model of dirofilariosis transmission for the Iberian Peninsula (Spain and Portugal) and the Balearic Islands (Spain).

The role of extracellular vesicles in cellular senescence.

Cellular senescence, an evolutionarily conserved mechanism that prevents the proliferation of damaged cells, is a very relevant cellular response involved in both physiological and pathological conditions. Even though senescent cells are stably growth arrested, they exhibit a complex and poorly understood secretory phenotype, known as senescence-associated secretory phenotype, composed of soluble proteins and extracellular vesicles (EVs). Extracellular vesicles were initially described as a waste management mechanism to remove damaged components of cellular metabolism, but increasing evidence shows that EVs could also play important roles in intercellular communication.

SOX9 Triggers Different Epithelial to Mesenchymal Transition States to Promote Pancreatic Cancer Progression.

Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers mainly due to spatial obstacles to complete resection, early metastasis and therapy resistance. The molecular events accompanying PDAC progression remain poorly understood. SOX9 is required for maintaining the pancreatic ductal identity and it is involved in the initiation of pancreatic cancer.

Radiogenomics: Hunting Down Liver Metastasis in Colorectal Cancer Patients.

Radiomics is a developing new discipline that analyzes conventional medical images to extract quantifiable data that can be mined for new biomarkers that show the biology of pathological processes at microscopic levels. These data can be converted into image-based signatures to improve diagnostic, prognostic and predictive accuracy in cancer patients. The combination of radiomics and molecular data, called radiogenomics, has clear implications for cancer patients' management.

The role of cellular senescence in tissue repair and regeneration.

The capacity to regenerate damaged or lost tissue varies widely along the animal kingdom and generally declines with aging of the organism. The gradual accumulation of senescent cells in tissues during aging has been causally involved in their reduced function at old age, and to be at the basis of age-related diseases. Recently, however, cellular senescence has been shown to play a positive role as a morphogenetic force modelling and promoting tissue development during embryogenesis, and to be responsible for tissue wound healing and repair.

RANK links senescence to stemness in the mammary epithelia, delaying tumor onset but increasing tumor aggressiveness.

Rank signaling enhances stemness in mouse and human mammary epithelial cells (MECs) and mediates mammary tumor initiation. Mammary tumors initiated by oncogenes or carcinogen exposure display high levels of Rank and Rank pathway inhibitors have emerged as a new strategy for breast cancer prevention and treatment. Here, we show that ectopic Rank expression in the mammary epithelia unexpectedly delays tumor onset and reduces tumor incidence in the oncogene-driven Neu and PyMT models.

SUMOylation modulates the stability and function of PI3K-p110β.

Class I PI3K are heterodimers composed of a p85 regulatory subunit and a p110 catalytic subunit involved in multiple cellular functions. Recently, the catalytic subunit p110β has emerged as a class I PI3K isoform playing a major role in tumorigenesis. Understanding its regulation is crucial for the control of the PI3K pathway in p110β-driven cancers.

Tumor Microenvironment in Metastatic Colorectal Cancer: The Arbitrator in Patients' Outcome.

Colorectal cancer (CRC) is one of the most common cancers in western countries. Its mortality rate varies greatly, depending on the stage of the disease. The main cause of CRC mortality is metastasis, which most commonly affects the liver.

The Jekyll and Hyde of Senescence in Cancer: TIMP1 Controls the Switch from Tumor-Controlling to Tumor-Promoting Senescence.

Cellular senescence is a response with two faces in cancer: it restricts tumor proliferation, but it can also promote cancer progression and metastasis. In this issue of Cancer Cell, Guccini et al. uncover the role of TIMP1 in prostate cancer allowing a switch from tumor-controlling to tumor-promoting senescence.

Developmentally-programmed cellular senescence is conserved and widespread in zebrafish.

Cellular senescence is considered a stress response imposing a stable cell cycle arrest to restrict the growth of damaged cells. More recently however, cellular senescence was identified during mouse embryo development at particular structures during specific periods of time. This programmed cell senescence has been proposed to serve developmental and morphogenetic functions and to potentially represent an evolutionary origin of senescence.

Author Correction: Identification and characterization of Cardiac Glycosides as senolytic compounds.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Merkel cells of human oral mucosa express the pluripotent stem cell transcription factor Sox2.

Merkel cells are neuroendocrine cells associated to a neural sensitive ending and localized primarily in the epidermis, although they are also found in oral mucosa. Sox2 or SRY-box2 is a key transcription factor important in the maintenance of embryonic neural crest stem cell pluripotency. Sox2 has been described in Merkel cells of skin and in Merkel cell carcinomas, but not specifically in oral Merkel cells.

Cellular Senescence: Defining a Path Forward.

Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential.

Cell senescence contributes to tissue regeneration in zebrafish.

Cellular senescence is a stress response that limits the proliferation of damaged cells by establishing a permanent cell cycle arrest. Different stimuli can trigger senescence but excessive production or impaired clearance of these cells can lead to their accumulation during aging with deleterious effects. Despite this potential negative side of cell senescence, its physiological role as a pro-regenerative and morphogenetic force has emerged recently after the identification of programmed cell senescence during embryogenesis and during wound healing and limb regeneration.

The development of cell senescence.

Cellular senescence was traditionally considered a stress response that protected the organism by limiting the proliferation of damaged and unwanted cells. However, the recent identification of developmentally-programmed cellular senescence during embryo development has changed our view of the process. There are now a number of examples of developmental senescence in evolutionary distant organisms ranging from mammals to fish, showing senescence at various sites during specific time windows of development.

Identification and characterization of Cardiac Glycosides as senolytic compounds.

Compounds with specific cytotoxic activity in senescent cells, or senolytics, support the causal involvement of senescence in aging and offer therapeutic interventions. Here we report the identification of Cardiac Glycosides (CGs) as a family of compounds with senolytic activity. CGs, by targeting the Na+/K+ATPase pump, cause a disbalanced electrochemical gradient within the cell causing depolarization and acidification.

Rag1 immunodeficiency-induced early aging and senescence in zebrafish are dependent on chronic inflammation and oxidative stress.

In mammals, recombination activating gene 1 (RAG1) plays a crucial role in adaptive immunity, generating a vast range of immunoglobulins. Rag1 zebrafish (Danio rerio) are viable and reach adulthood without obvious signs of infectious disease in standard nonsterile conditions, suggesting that innate immunity could be enhanced to compensate for the lack of adaptive immunity. By using microarray analysis, we confirmed that the expression of immunity- and apoptosis-related genes was increased in the rag1 fish.